As part of a study of the pathogenesis of chronic inflammation initiated by a picornavirus, we have tracked the presence of viral genome by in situ hybridization after infection of mice with encephalomyocarditis virus, strain EMC-221A. Viral nucleic acid can be found in cells at least a week or two after disappearance of culturable virus. Inflammation disappears in some organs when virus does, but persists in others for much longer periods. We have worked out a variation of the polymerase chain reaction to detect persistent viral nucleic acid sequences with much higher sensitivity.